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2070009-72-0

中文名稱 2070009-72-0
英文名稱 D8-MMAE
CAS 2070009-72-0
分子式 C39H59D8N5O7
分子量 726.028
MOL 文件 2070009-72-0.mol
更新日期 2024/11/15 18:20:32
2070009-72-0 結(jié)構(gòu)式 2070009-72-0 結(jié)構(gòu)式

基本信息

中文別名
微管蛋白聚合抑制劑(D8-MMAE)
英文別名
D8-MMAE
D8-Monomethyl auristatin E

物理化學(xué)性質(zhì)

儲存條件Store at -20°C,unstable in solution, ready to use.
溶解度DMSO : 100 mg/mL (137.74 mM; Need ultrasonic)
形態(tài)Solid
顏色White to off-white

常見問題列表

生物活性
D8-MMAE (D8-Monomethyl auristatin E) 是氘代標(biāo)記的 MMAE。MMAE 是一種 tubulin 抑制劑,抑制有絲分裂。
靶點

Auristatin

體外研究

Antibody-drug conjugates (ADC) comprise targeting antibodies armed with potent small-molecule payloads. ADCs are generated to target different receptors on the anaplastic large cell lymphoma line L-82, but delivered the same cytotoxic payload (monomethyl auristatin E, MMAE), and the intracellular concentration of released MMAE correlated with in vitro ADC-mediated cytotoxicity independent of target expression or drug:antibody ratios. LC-MS is used to measure the concentration of MMAE in a parallel cohort of L-82 tumors with an identical treatment regimen. Although tumor volume is not different among treatment groups 3 days after dose, the intratumoral MMAE measurement reveals two patterns. First, intratumoral MMAE concentration increases proportionally to the ADC dose, which correspondes to stronger antitumor activity. Second, the intratumoral MMAE concentration obtained from treatment with both cOKT9-vcMMAE and cAC10-vcMMAE is similar at each dose, consistent with the observation that tumor responded similarly to these two ADCs.

體內(nèi)研究

Intratumoral MMAE concentrations consistently correlates with the extent of tumor growth inhibition in tumor xenograft models. IHC analysis reveals that nonbinding control-treated tumors consist of both CD30 + and CD30 - cells, presumably because they do not kill either CD30 + or CD30 - Karpas 299 cells. Only CD30 - cells are found in cAC10-vcMMAF-treated tumors, illustrating that cAC10-vcMMAF eliminates most CD30 + cells. Interestingly, the two tumors that relapses from cAC10-vcMMAE treatment are also found to be CD30 - by the end of study, indicating a small fraction of CD30 - cells might have escaped from bystander killing in these two remaining tumors.

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